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曲妥珠单抗所致心脏毒性的预防和治疗干预措施:系统评价与荟萃分析的伞状综述

Interventions for prevention and treatment of trastuzumab-induced cardiotoxicity: an umbrella review of systematic reviews and meta-analyses.

作者信息

Wang Yunfang, Xu Jianguo, Xie Yafei, Zhou Dan, Guo Mingyue, Qin Yu, Yi Kang, Tian Jinhui, You Tao

机构信息

Department of Endocrinology, Gansu Provincial Hospital, Lanzhou, China.

Evidence-Based Medicine Center, School of Basic Medical Sciences, Lanzhou University, Lanzhou, China.

出版信息

Front Pharmacol. 2024 Dec 5;15:1479983. doi: 10.3389/fphar.2024.1479983. eCollection 2024.

Abstract

BACKGROUND

Trastuzumab therapy for HER2-positive cancers is associated with cardiotoxicity. This umbrella review synthesizes evidence from systematic reviews and meta-analyses on cardioprotective interventions during trastuzumab treatment.

METHODS

A comprehensive search was conducted in PubMed, Embase, Cochrane Library, and Web of Science. Systematic reviews and meta-analyses examining cardioprotective interventions in patients receiving trastuzumab were included. The methodological quality was assessed using the AMSTAR-2 tool. Data on cardiac events, treatment interruptions, left ventricular ejection fraction (LVEF) changes, and exercise interventions were synthesized.

RESULTS

Ten systematic reviews met the inclusion criteria. Statins demonstrated the strongest cardioprotective effect (RR = 0.47, 95% CI: 0.26-0.84), potentially preventing more than half of cardiac events during trastuzumab therapy, followed by beta-blockers (RR = 0.61, 95% CI: 0.39-0.93). Beta-blockers and ACEIs effectively reduced treatment interruptions, enabling approximately 40% more patients to maintain treatment continuity (RR = 0.63, 95% CI: 0.47-0.86). Among non-pharmacological interventions, structured exercise programs showed significant benefits in preserving cardiac function, demonstrating meaningful improvements in resting LVEF (WMD = -3.27%, 95% CI: -5.86 to -0.68).

DISCUSSION

This review demonstrates that cardioprotective interventions, particularly statins and beta-blockers, significantly reduce the risk of cardiac complications during trastuzumab therapy. The positive impact on cardiac events and treatment interruptions suggests these interventions may enhance overall treatment efficacy by allowing more patients to complete their prescribed course.

CONCLUSION

Evidence strongly supports the systematic implementation of cardioprotective strategies in clinical practice, particularly statins and beta-blockers, as part of routine care protocols for patients receiving trastuzumab therapy. These interventions demonstrate significant potential in preventing cardiac complications and maintaining treatment continuity. Further research should focus on optimizing personalized approaches and evaluating long-term outcomes.

摘要

背景

曲妥珠单抗治疗HER2阳性癌症与心脏毒性相关。本伞状综述综合了来自系统评价和荟萃分析的关于曲妥珠单抗治疗期间心脏保护干预措施的证据。

方法

在PubMed、Embase、Cochrane图书馆和Web of Science中进行了全面检索。纳入了检查接受曲妥珠单抗治疗患者心脏保护干预措施的系统评价和荟萃分析。使用AMSTAR-2工具评估方法学质量。综合了关于心脏事件、治疗中断、左心室射血分数(LVEF)变化和运动干预的数据。

结果

十项系统评价符合纳入标准。他汀类药物显示出最强的心脏保护作用(RR = 0.47,95%CI:0.26 - 0.84),可能预防曲妥珠单抗治疗期间超过一半的心脏事件,其次是β受体阻滞剂(RR = 0.61,95%CI:0.39 - 0.93)。β受体阻滞剂和ACEIs有效减少了治疗中断,使多约40%的患者能够维持治疗连续性(RR = 0.63,95%CI:0.47 - 0.86)。在非药物干预中,结构化运动计划在保护心脏功能方面显示出显著益处,静息LVEF有显著改善(WMD = -3.27%,95%CI:-5.86至-0.68)。

讨论

本综述表明,心脏保护干预措施,特别是他汀类药物和β受体阻滞剂,可显著降低曲妥珠单抗治疗期间心脏并发症的风险。对心脏事件和治疗中断的积极影响表明,这些干预措施可能通过使更多患者完成规定疗程来提高总体治疗效果。

结论

证据强烈支持在临床实践中系统实施心脏保护策略,特别是他汀类药物和β受体阻滞剂,作为接受曲妥珠单抗治疗患者常规护理方案的一部分。这些干预措施在预防心脏并发症和维持治疗连续性方面显示出巨大潜力。进一步的研究应侧重于优化个性化方法并评估长期结果。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f2fa/11655193/2d6a8acf4da6/fphar-15-1479983-g001.jpg

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